Connective Tissue Diseases

Digital Lecture Series : Chapter 19

Dr. Vinitha Varghese Panicker

Associate Professor, Department of Dermatology,
Amrita Institute of Medical Sciences
& Research Centre, Cochin
 CONTENTS

 Lupus erythematosus (DLE / SCLE / SLE)

 Scleroderma (Morphoea / Systemic Sclerosis)
 Dermatomyositis / Polymyositis
 Rheumatoid arthritis
 Sjogren’s syndrome
 Mixed connective tissue disease
 Antiphospholipid antibody syndrome
 MCQs
 Photo Quiz
 Lupus Erythematosus (LE)- Types

Cutaneous lupus erythematosus is classified into three subtypes:

Acute cutaneous lupus erythematosus (ACLE):

 Malar rash, Morbilliform rash, bullous lesions
Subacute cutaneous lupus erythematosus (SCLE):
 Annular, Papulosquamous
Chronic cutaneous lupus erythematosus (CCLE):
 Discoid Lupus Erythematosus
 Pathogenesis of Cutaneous LE

 Genetic Factors - HLA susceptibilty

 Environmental triggers -
UV exposure induces cytokine release and apoptosis.
 Immunologic factors -
Malfunction of T regulatory cells (T reg)
Role of IL-18
 Acute Cutaneous LE

Localised ACLE -
 Characteristic butterfly facial rash

Generalised ACLE -
 Widespread maculopapular rash in a photo-distributed pattern
 Subacute Cutaneous LE

 Non - scarring; papulosquamous / annular polycyclic lesions.

 Vesiculation, crusting, hypopigmentation, telangiectasia, alopecia,
photosensitivity, Raynaud’s phenomenon.
 Sites : above waist, neck, arms.
 Systemic involvement 35%.
 ANA, anti - Ro, anti - La.
 Chronic: Discoid Lupus Erythematosus (DLE)

 DLE is a relatively benign disorder of the skin, characterized by well

defined, reddish, scaly patches which tend to heal with atrophy,
scarring and pigmentary changes.
 The histology is characteristic.
 Female : Male - 2 : 1
 Onset - second-fourth decade of life
 Family history : 4%
 Genetic factors - HLA B7, B8
Discoid rash
 Diagnosis

 Histopathology :
Epidermal atrophy, basal layer liquefaction, lymphocytic dermal
infiltrate and ‘Civatte bodies’.

 Differential diagnosis :
Polymorphous Light eruption, Morphoea, Lichen planus, Lupus
vulgaris, Sarcoidosis.
 Systemic LE

 Definition :
A systemic disease with immunopathological abnormalities affecting
various organs particularly the skin, joints and vasculature.
• Females > males
• Onset: early adult life
 Clinical features

 Fever (52%), lymphadenopathy

 Arthritis (84%) and arthralgia
 Cutaneous lesions : specific and non -specific
 Raynaud’s phenomenon
 Renal - nephritis or as nephrotic syndrome.
 Lung-pleural effusion, alveolitis, interstitial lung disease
 Cardiac-pericardial effusion, myocardial infarction, Libman-sacks
endocarditis
 CNS involvement : migraine, epilepsy, neuropathy.
 GIT and hepatic involvement : vasculitis of gut, ascites, pancreatitis,
autoimmune hepatitis.
 Splenomegaly, hepatitis, cirrhosis.
 Hematologic-Anemia, leukopenia, Thrombocytopenia.
 Ocular - Conjunctvitis, episcleritis, Retinal vasculitis.
 Cutaneous lesions

 LE specific
• ACLE – Malar rash
• SCLE – Annular, Psoriasiform
• CCLE – Plaque
Lupus panniculitis
Hypertrophic
Tumid CCLE
Chilblain CCLE
Mucosal CCLE
Malar rash Oral ulcer
 LE Non specific lesions

 Vascular: Telangiectasia, Purpura,  Bullous lesions

Thrombophlebitis, Raynauds  Urticaria
phenomenon, livedo reticularis,  Pigmentary abnormalities
erythema multiforme
 Sclerodactyly and
 Alopecia: Lupus hair, Alopecia sclerodermatous changes
Areata, Scarring Alopecia
 Papulonodular mucinosis
 Mucus membrane lesions
 Anetoderma
 Nail changes
 Lichen planus
 Calcinosis cutis
 Porphyria cutanea tarda

Contd…
 Special subsets of LE

 SLE in pregnancy
 Neonatal LE
 Drug induced LE
 Childhood SLE
 Rowell’s syndrome
 Investigations

 CBC : anemia , leukopenia , thrombocytopenia

 ESR : raised
 Urine analysis, BUN, S. Creatinine
 False positive VDRL & RA factor
 LE cell test
 ANA
 Anti-DNA, anti-Sm, anti-histone, cryoglobulins, serum complement
levels
 DIF – Lupus band test
 ANA Patterns

ANA PATTERN PREDOMINANT ANTIGEN DISEASE

PERIPHERAL nDNA SLE

HOMOGENOUS nDNA, histones SLE

NUCLEOLAR Nucleolar RNA SSc, SLE

CENTROMERE Kinetophore CREST syndrome

SPECKLED Various RNPs MCTD, SLE, SSc,

Sjogrens syndrome
 American College of Rheumatology, ACR criteria

 Malar rash
 Discoid rash
 Photosensitivity
 Oral ulcers
 Non–erosive arthritis
 Serositis : pleurisy or pericarditis
 Renal disorder : persistent proteinuria (>0.5g/day) or cellular casts
 Neurological disorders : seizures or psychosis

Contd…
 American College of Rheumatology, ACR criteria

 Haematological disorders - heamolytic anemia or leukopenia

(<4000/mm3) or lymphopenia (<1500/mm3) or thrombocytopenia
(<1,00,000/mm3).
 Immunological disorder - LE cells, or anti-dsDNA antibody or anti Sm
antibody or false positive VDRL.
 Antinuclear antibodies.
4 or more criteria are required for definitive diagnosis.
 SLICC CRITERIA
(Systemic Lupus International Collaborating clinics)
Clinical and Investigative criteria
 Acute or subacute cutaneous lupus
 Chronic cutaneous LE
 Oral/nasal ulcers
 Non Scarring Alopecia
 Inflammatory synovitis
 Serositis
 Renal-Rbc casts, urine protein/creatinine atleast 500 mg protein/24 hr
 Neurologic
 Hemolytic anemia
 Leukopenia (<4000/mm) atleast once or lymphopenia (<1000/mm)
atleast once.
Contd…
 SLICC CRITERIA
(Systemic lupus International Collaborating clinics)
 Thrombocytopenia
 Immunologic criteria –
• ANA above reference range
• Antids DNA above lab ref range
• Anti-Sm
• Antiphospholipid antibody
• Low complement-C3,C4,CH50
• Direct Coombs test in absence of hemolytic anemia

Patient may be classified as having SLE if: patient has biopsy proven lupus
nephritis with ANA or ds DNA antibodies or if they satisfy 4 criteria
including at least one clinical/ one immunologic .
 Treatment

Mild disease
 NSAIDs, topical therapy, antimalarials

Severe disease
 Systemic steroids
 Steroid sparing immunosuppressants - Azathioprine,
Cyclophosphamide, Mycophenolate mofetil
 Biologics - Rituximab-monoclonal ab targeting CD20 receptor protein
on surface of B cells-mainly for arthritis and proteinuria.
 Morphoea

Definition :
 Sclerosis confined to the skin, localised or generalized is termed as
‘Morphoea’.
 Female : Male - 3 : 1
 Onset : 20 - 40 years;
 Precipitating factors : Trauma, vaccination, radiotherapy, hormonal
factors, borrelia infection, measles, silicone implants.
 Types of Morphea

 Plaque type - morphea en plaque, guttate morphea, keloid (nodular)

morphea, atrophoderma of Pasini and Pierni.
 Generalised morphea
 Bullous morphea
 Linear morphea - linear type, en coup de sabre, progressive hemifacial
atrophy.
 Deep Morphea - Subcutaneous morphea, eosinophilic fasciitis, morphea
profundus, disabling pansclerotic morphea.
 Clinical features

Plaque type -
 Round or oval indurated plaques with lilac border.
 Heals slowly with residual hyperpigmentation.
 Multiple, asymmetrical distribution.
 Sites : trunk, limbs, face.
Linear Morphea -
Plaques of morphea in linear arrangement mainly on limbs
Type on frontoparietal region - en coup de sabre
En-Coup-de-Sabre
 Treatment

 Triamcinolone acetonide, 10 - 40 mg/ml intralesional injection

 Penicillamine : 300 - 600 mgs / day
 Diphenylhydantoin
 Systemic steroids
 Cyclosporine,
 Topical Vit. D3 analogues
 Topical tacrolimus
 Phototherapy, plasmapheresis, physiotherapy, plastic surgery
 Systemic Sclerosis

 Systemic sclerosis is a multisystem autoimmune disorder

characterized by vascular abnormalities, connective tissue sclerosis
and atrophy .
 Females : Males - 5.2 : 1
 Onset : Fourth decade
 Etiology and pathogenesis : complex autoimmune disease
charecterised by immune activation, fibrosis of skin and obliterative
vasculopathy.
 Classification According to Skin sclerosis

 Limited Cutaneous Scleroderma - skin sclerosis of fingers

(sclerodactyly) with or without mild sclerosis of face, neck and
armpits.
 Diffuse cutaneous Scleroderma - Diffuse and truncal sclerosis.
 Immediate cutaneous scleroderma - Sclerosis of upper and lower
limbs, neck and face without truncal involvement.
 Sine scleroderma SSc - Absence of cutaneous sclerosis with typical
visceral organ involvement, capillaroscopy changes and serum
autoantibodies.
 Cutaneous features

 Raynaud’s phenomenon
 ‘Hide-bound’ skin
 Classical sclerodermoid facies- “mask-like” face, pinched or beak-like
appearance of nose, radial furrows around the mouth and thinning
of the upper lip
 Pigmentation – mottled or hyperpigmentation
 Swelling of hands & joints, atrophy
 Finger and leg ulcers, digital gangrene, stellate scars
 Nail fold telangiectasias
 Calcinosis
 Features of syctemic sclerosis

Classical sclerodermoid facies Pitted scars

 Systemic Features

 Gastrointestinal and Hepatic -

Esophageal Dysfunction, malabsorption, primary biliary cirrhosis,
Autoimmune hepatitis.
 Arthritis, tendon friction rubs.
 Renal-scleroderma renal crisis (most severe).
 Lung-Interstitial lung disease, Pulmonary hyertension.
 Cardiac-myocardial disease, pericardial involvement.
 Muscle-SSc Associated myopathy more common in diffuse SSc.
 Diagnosis

2013 ACR/EULAR criteria -

 Skin thickening of the fingers extending proximal to MCP jts is
sufficient to diagnose the patient as SSc.
 If this is not present seven other features apply with for varying
weights for each -
• Skin thickening of fingers
• Finger tip lesions
• Telangiectasia
• Abnormal nail fold capillaries
• Interstitial lung disease or pulmonary artery hypertension
• Raynaud’s phenomenon
• Ssc related autoantibodies (anticentromere, antitopoisomerase,
antiRnp-3)
 Investigations

 Serology - ANA, anticentromere antibodies, anti-Scl 70 antibody

 Pulmonary Function test -Detect fibrotic changes
 Histopathology - Hyalinization and homogenisation of collagen,
dermal lymphocytic infiltrate.
 ECG- To detect rhythm and conduction abnormalities.
 ECHO- Detect pulmonary artery hypertension.
 GI involvement- Esophageal manometry, endoscopy, barium studies.

Contd…
 Treatment

 Use of gloves
 For Raynauds - nifedepine (mild cases), sildenafil, iloprost, low
molecular weight dextran.
 Corticosteroids
 Immunosuppressants : Methotrexate, Cyclophosphamide
 Penicillamine, colchicine, interferons.
 Symptomatic treatment for pulmonary, cardiac, renal and GIT
symptoms.
 Dermatomyositis

 An idiopathic inflammatory myopathy characterised by muscle

weakness and cutaneous eruption.
 Females > males
 Bimodal peak during childhood and then between 50-70 yrs
 ETIOLOGY
 HLA-B8, DRB1*0301, DQA1*0501, DQA1 *0301
 Infections - Gr A Beta hemolytic streptoccoci, toxoplasma, coxsackie
 UV radiation exposure
 Drugs-d penicillamine, tamoxifen, INH, penicillins
 Cutaneous features

 Pathognomic skin manifestation - Gottrons papules and Gottron’s

sign.
 Gottrons papules - violaceous papules overlying the dorsal
interphalangeal and metacarpophalangeal joints, elbows and knees.
 Gottrons sign - erythematous or violcaeuos erythema with or without
edema.
 Characteristic skin lesions - heliotrope erythema and macular
violaceous erythema over the deltoids, posterior shoulders, nape of
neck, upper chest (V sign), forehead and dorsa of hands.
 Cutaneous calcinosis more common in JDM, 40-75% cases.
Heliotrope Gottron’s papules
 Systemic manifestations

 Muscle :
Progressive symmetric proximal myopathy; pharyngeal and
respiratory muscles may be involved.
 Joints :
Non erosive arthritis, usually an early manifestation.
 Pulmonary :
Aspiration pneumonia, Interstitial lung disease, Hypoventilation.
 Cardiac : Arrythmia , conduction abnormalities myocarditis.
 Gastrointestinal : Dysphagia, esophageal reflux.
 Criteria for diagnosis (Bohan and Peter)

 Symmetric muscle weakness

 Elevation of skeletal muscle enzymes
 Abnormal EMG results
 Muscle biopsy results
 Typical rash of DM

Definite diagnosis : characteristic skin rash + ¾ remaining criteria .

 Investigations

 Muscle enzymes : CK, SGOT, SGPT, LDH, S. Aldolase

 CK - MM fraction most specific for skeletal muscle
 Muscle biopsy - definitive diagnosis
 EMG
 MRI - may detect subclinical muscle involvement .
 Serology : ANA, anti Jo - 1, anti - Mi 2
 Treatment

 Corticosteroids
 Immunosuppressants : Methotrexate, Mycophenolate mofetil
Cyclophosphamide, Azathioprine
 Methotrexate considered first choice among adjuvants
 IV Ig - refractory cases
 Rituximab
 Exercise and physical therapy
 Cutaneous lesions - Sunscreens, Hydroxychloroquine,
 Calcinosis - alendronate, diltiazem, excision of large lesions
 Mixed Connective Tissue Disease

 Affects predominantly females

 Features of SLE, systemic sclerosis, dermatomyositis, polymyositis
 Specific antibody to U1-RNP.
 Raynaud’s phenomenon, arthritis, arthralgia, sausage shaped fingers,
swelling of hands, photosensitivity, SCLE like rash.
 Abnormal oesophageal motility, impaired pulmonary diffusing
capacity, myositis, aseptic meningitis, psychosis, trigeminal
neuropathy.
 Sjogrens Syndrome

 Xerostomia with keratoconjunctivitis sicca

Cutaneous features :
 Xerosis, Generalised pruritus, Loss of sweating, Diffuse alopecia,
Recurrent annular erythema.
 Raynaud’s phenomenon, Non thromobocytopenic Purpura, Urticarial
vasculitis, necrotising vasculitis, splinter hemorrhages, gangrene.
 Cutaneous Manifestations of Rheumatoid Arthritis
Specific manifestations :
 Rheumatoid Nodules - most frequent extra-articular manifestation.
 Granulomatous dermatitis - linear erythematous to violaceous
subcutaneous bands in axilla, trunk, inner aspect of thighs.
 Rheumatoid Vasculitis - Ulcers, digital infarcts, nail fold infarcts
(Bywaters lesions)
 Pyoderma gangrenosum
 Feltys syndrome
 Juvenile onset RA
Non Specific Manifestations :
 Palmar erythema, sclerodactyly like changes, periungual erythema,
splinter hemorhages, bluish discoloration of fingers.
 Antiphospholipid Antibody Syndrome

 Primary and Secondary

 Secondary causes include - autoimmune connective tissue diseases,
Takayasu’s arteritis, bacterial and viral infections, malignancies,
dialysis in renal failure.
 Approx 40% have cutaneous manifestations.
 Livedo reticularis most common.
 Others - necrotising vasculitis, thrombophlebitis, cutaneous ulcers,
gangrene, necrosis, purpura, erythematous macules, ecchymoses,
painful skin nodules, anetoderma, atrophie - blanche like lesions,
subungual splinter hemorrhages.
 MCQs

Q.1) Carpet tack sign is seen in

A. SCLE
B. DLE
C. SLE
D. Bullous LE

Q.2) Rowells syndrome is

E. Lupus panniculitis
F. LE and EM like lesions
G. LE and Scleroderma
H. Neonatal LE
 MCQs

Q.3) Pathognomic skin lesion of Dermatomyositis

A. Gottron’s papules
B. Heliotrope erythema
C. Shawl sign
D. Poikiloderma vasculare

Q.4) Water melon stomach is seen in

E. SLE
F. Systemic Sclerosis
G. Dermatomyositis
H. MCTD
 MCQs

Q.5) 53 year old lady presents to the medical assessment unit with a flu-like
illness and myalgia. In the last few days she has noticed a rash across her
back. She has no other symptoms. On examination she looks unwell.
There is an erythematous rash across her back. She has grade 4/5
weakness proximally. Her CK which is elevated at 1052 IU/l. Her renal
function is normal. What is the diagnosis?
A. SLE
B. Systemic Sclerosis
C. Dermatomyositis
D. Antiphospholipid antibody syndrome
 Photo Quiz

Q. Identify the condition.

 Photo Quiz

Q. Identify the condition.

 Photo Quiz

Q. Identify the condition.

Thank You!